(1) Goals of project: - To determine the contribution of anti-HLA class II autoantibodies, generated in HIV-1 infected individuals due to homology with gp41, to their disease progression. - To determine whether uninfected volunteers, vaccinated with HIV-1 envelope-based vaccine develop anti-HLA class II autoantibodies. (2) Experimental approach: - Sequential Sera from HIV-1 patients participating in the MACS study are tested for the presence of cross-reactive anti-gp41/class II autoantibodies by ELISA. Their antibody titers are then correlated with their disease progression rate in terms of CD4 cell counts and clinical symptoms. - Sera from vaccinated volunteers are provided through the DAIDS group. Pre-immune and post-vaccination sera are screened for the presence of anti-class II autoantibodies. Titers are then correlated with the overall response to the vaccine and the to the vaccine dose used. (3) Major Findings: - In a cohort of HIV-1 infected hemophiliacs, and patients enrolled in the MACS study, high titers of CRab was found to correlate with rapid progression (2-4 yrs) to full blown AIDS. CRab Appear 2-3 yrs prior to CD4 decline. True stable patients have very low frequency of anti-class II CRab. We are currently continuing to study sera from patients in the MACS study to determine if the presence of CRab autoantibodies can be used as a predictive measurement preceding clinical deterioration. - We also tested sera from various vaccine groups who were immunized with subunit vaccines containing the gp41/HLA class II homologous region, for the presence of CRab. One seropositive vaccine group showed marked elevation in CRab titers following vaccination.